Issued by
National Institute of Environmental Health Sciences (NIEHS)
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The NIEHS Division of Extramural Research and Training (DERT) and the NHLBI Division of Cardiovascular Sciences (DCVS) are seeking input for identification of key biological mechanisms/pathways of the combined effects of chemical and non-chemical stressors associated with atherosclerosis. Information provided will be used in planning a workshop for FY 2018 to help inform the development of intramural and extramural research efforts that address the combined health effects of environmental chemical and non-chemical stressors associated with atherosclerosis, a known multi-factorial disease. Input from all interested parties is welcome including the lay public, environmental health researchers, health professionals, educators, policy makers, industry, and others.

Background
The NIEHS mission is to reduce the burden of human illness and disability by understanding how the environment influences the development and progression of human disease. To accomplish this, the NIEHS supports research and professional development in environmental health sciences, clinical research, and public health. DERT plans, directs and evaluates the NIEHS grant program, which supports research and research training in environmental health. It develops program priorities and recommends funding levels to assure maximum utilization of available resources in attainment of NIEHS objectives. Through cooperative relationships with NIH and with public and private institutions and organizations, DERT maintains an awareness of national research efforts and assesses the need for research and research training in environmental health.

The NHLBI mission is to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives. The NHLBI stimulates basic discoveries about the causes of disease, enables the translation of basic discoveries into clinical practice, fosters training and mentoring of emerging scientists and physicians, and communicates research advances to the public. It creates and supports a robust, collaborative research infrastructure in partnership with private and public organizations, including academic institutions, industry, and other government agencies. The Institute collaborates with patients, families, health care professionals, scientists, professional societies, patient advocacy groups, community organizations, and the media to promote the application of research results and leverage resources to address public health needs. The NHLBI also collaborates with international organizations to help reduce the burden of heart, lung, and blood diseases worldwide.

The evaluation of cumulative and combined human health effects from multiple environmental exposures (i.e., chemical and non-chemical) represents a special challenge to the research community due to the inherent complexity of the topic. Moreover, a critical research area which requires further exploration is the biological mechanisms/pathways by which exposure to both environmental chemicals (e.g., air pollution, polycyclic aromatic hydrocarbons, metals, polychlorinated biphenyls , pesticides, and endocrine disrupting chemicals) and non-chemical stressors (e.g., psychosocial, lifestyle, quality-of-life, poor nutrition, infectious agents, physical stressors) over time leads to health effects and the roles they may play in the development of diseases known to be associated with these stressors (e.g., cancer, cardiac, metabolic, neurological, etc.). For the purposes of this RFI, combined exposures pertain to any set of environmental chemicals and non-chemical stressors that may contribute jointly to adverse human health outcomes, irrespective of whether people are exposed to the chemical(s)/non-chemical stressors at the same/different times or through similar/distinct sources or routes. Some of the other areas requiring further research on this complex topic includes: a better understanding of both the composition of real-world exposure to chemical and non-chemical stressors, the biological interactions between chemical and non-chemical stressors, statistical approaches to address the potential interactions of these complex exposures, and the development and validation of predictive models of combined exposure toxicity to characterize the hazard associated with these combined exposures.

This currently proposed workshop will bring together experts to discuss the state-of-the-science pertaining to underlying biological mechanisms/pathways associated with, when combined, chemical and non-chemical stressors in relation to atherosclerosis. Atherosclerosis can lead to cardiac infarction and stroke and is a foremost candidate for identifying health effects associated chemical and non-chemical stressors since much is known about the morbidity and mortality of this multifactorial disease. In addition, cardiovascular disease is the leading cause of death in the US and its morbidity is associated with significant health care and economic burdens.

The overarching goals of the workshop are as follows: to serve as a model to study environmental chemical and non-chemical stressors in the etiology of atherosclerosis; discuss the state-of-the-science pertaining to underlying biological mechanisms/pathways associated with, when combined, chemical and non-chemical stressors in relation to atherosclerosis, identify research gaps in biological mechanisms/pathways leading to atherosclerosis; characterize qualitative and quantitative (i.e., “dose-response) impacts of exposure to the combination of chemical and non-chemical stressors; encourage sharing of data between grantees conducting chemical and non-chemical stressor research; provide opportunities for collaborations among the atherosclerosis research community; and develop new hypotheses of underlying mechanisms/pathways of atherosclerosis. In addition, this workshop will foster discussion on the approaches, infrastructure, and resources needed to make progress and to identify new scientific opportunities in the field of combined exposures research. The workshop will bring together experts from multiple disciplines including, but not limited to, experts in the field of: atherosclerosis research, chemical and non-chemical stressors, exposure assessment, biology, toxicology, epidemiology, biostatistics, risk assessment, and regulatory science.

Information Requested

DERT and DCVS request information regarding the key biological mechanisms/pathways associated with chemical and non-chemical stressors leading to atherosclerosis. Responses to any or all of the questions below are invited from interested individuals/groups, including, but not limited to, the environmental health research community, health professionals, educators, policy makers, industry, and the public.

Environmental chemicals known to affect key biological mechanisms /pathways leading to atherosclerosis and which key biological mechanisms/pathways are affected by these chemicals.

Non-chemical stressors known to affect key biological mechanisms /pathways leading to atherosclerosis and which key biological mechanisms/pathways are affected by these non-chemical stressors.

Key biological mechanisms/pathways of atherosclerosis affected by the combined exposures of chemical and non-chemical stressors.

Qualitative and quantitative (i.e., “dose-response”) impacts of exposure to the combination of chemical and non-chemical stressors and technical challenges in quantitative assessment of these exposures or impacts.

New technologies and innovative research approaches that could be leveraged to address these underlying knowledge gaps.

Responses

All responses to information requested in this RFI are voluntary. Responses should be submitted on-line at the webpage by January 31, 2017.

Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAAA staff, and individual feedback will not be provided to any responder. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information

Acknowledgement of receipt of responses will be provided through the webpage but respondents will not be notified of the Government’s assessment of the information received.